Invasive infections by Staphylococcus aureus are now common and life-threatening. As methicillin-resistant (MRSA) or vancomycin-refractory (VISA, VRSA) strains are leading community-acquired and nosocomial pathogens, invasive S. aureus infections now have attributable mortalities approaching 40%-50%, even with modern therapeutics. Costs associated with such infections now exceed $2 billion per year in the US alone. Such a clear and present threat to public health emphasizes the urgency to address this unmet medical need. Yet, remarkably little is known of pharmacologic approaches to minimize resistance or enhance antibiotic efficacy vs. MRSA. As an alternative to the time and cost of developing new anti-staphylococcal antibiotics, there is a need to discover adjunctive combinations that mitigate resistance and optimize therapeutic outcomes to serious or life threatening bacterial infections, including methicillin-resistant SA (MRSA), that are increasingly refractory to most if not all forms of conventional antimicrobial therapy (pan-resistant). The present invention meets this need and provides related advantages.